Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex

In human patients, a wide range of mutations in keratin (K) 5 or K14 lead to the blistering skin disorder epidermolysis bullosa simplex. Given that K14 deficiency does not lead to the ablation of a basal cell cytoskeleton because of a compensatory role of K15, we have investigated the requirement for the keratin cytoskeleton in basal cells by inactivating the K5 gene in mice. We report that the K5−/− mice die shortly after birth, lack keratin filaments in the basal epidermis, and are more severely affected than K14−/− mice. In contrast to the K14−/− mice, we detected a strong induction of the wound-healing keratin K6 in the suprabasal epidermis of cytolyzed areas of postnatal K5−/− mice. In addition, K5 and K14 mice differed with respect to tongue lesions. Moreover, we show that in the absence of K5 and other type II keratins, residual K14 and K15 aggregated along hemidesmosomes, demonstrating that individual keratins without a partner are stable in vivo. Our data indicate that K5 may be the natural partner of K15 and K17. We suggest that K5 null mutations may be lethal in human epidermolysis bullosa simplex patients.

Types of evolutionary stability and the problem of cooperation.

The evolutionary stability of cooperation is a problem of fundamental importance for the biological and social sciences. Different claims have been made about this issue: whereas Axelrod and Hamilton's [Axelrod, R. & Hamilton, W. (1981) Science 211, 1390-1398] widely recognized conclusion is that cooperative rules such as "tit for tat" are evolutionarily stable strategies in the iterated prisoner's dilemma (IPD), Boyd and Lorberbaum [Boyd, R. & Lorberbaum, J. (1987) Nature (London) 327, 58-59] have claimed that no pure strategy is evolutionarily stable in this game. Here we explain why these claims are not contradictory by showing in what sense strategies in the IPD can and cannot be stable and by creating a conceptual framework that yields the type of evolutionary stability attainable in the IPD and in repeated games in general. Having established the relevant concept of stability, we report theorems on some basic properties of strategies that are stable in this sense. We first show that the IPD has "too many" such strategies, so that being stable does not discriminate among behavioral rules. Stable strategies differ, however, on a property that is crucial for their evolutionary survival--the size of the invasion they can resist. This property can be interpreted as a strategy's evolutionary robustness. Conditionally cooperative strategies such as tit for tat are the most robust. Cooperative behavior supported by these strategies is the most robust evolutionary equilibrium: the easiest to attain, and the hardest to disrupt.

Electrical investigation of p-type 4H-SiC heavily doped by ion implantation

In the last decades, an increasing interest in the research field of wide bandgap semiconductors was observed, mostly due to the progressive approaching of silicon-based devices to their theoretical limits. 4H-SiC is an example among these, and is a mature compound for applications. The main advantages offered 4H-SiC in comparison with silicon are an higher breakdown field, an higher thermal conductivity, a higher operating temperature, very high hardness and melting point, biocompatibility, but also low switching losses in high frequencies applications and lower on-resistances in unipolar devices. Then, 4H-SiC power devices offer great performance improvement; moreover, they can work in hostile environments where silicon power devices cannot function. Ion implantation technology is a key process in the fabrication of almost all kinds of SiC devices, owing to the advantage of a spatially selective doping. This work is dedicated to the electrical investigation of several differently-processed 4H-SiC ion- implanted samples, mainly through Hall effect and space charge spectroscopy experiments. It was also developed the automatic control (Labview) of several experiments. In the work, the effectiveness of high temperature post-implant thermal treatments (up to 2000°C) were studied and compared considering: (i) different methods, (ii) different temperatures and (iii) different duration of the annealing process. Preliminary p + /n and Schottky junctions were also investigated as simple test devices. 1) Heavy doping by ion implantation of single off-axis 4H-SiC layers The electrical investigation is one of the most important characterization of ion-implanted samples, which must be submitted to mandatory post-implant thermal treatment in order to both (i) recover the lattice after ion bombardment, and (ii) address the implanted impurities into lattice sites so that they can effectively act as dopants. Electrical investigation can give fundamental information on the efficiency of the electrical impurity activation. To understand the results of the research it should be noted that: (a) To realize good ohmic contacts it is necessary to obtain spatially defined highly doped regions, which must have conductivity as low as possible. (b) It has been shown that the electrical activation efficiency and the electrical conductivity increase with the annealing temperature increasing. (c) To maximize the layer conductivity, temperatures around 1700°C are generally used and implantation density high till to 10 21 cm -3 . In this work, an original approach, different from (c), is explored by the using very high annealing temperature, around 2000°C, on samples of Al + -implant concentration of the order of 10 20 cm -3 . Several Al + -implanted 4H-SiC samples, resulting of p-type conductivity, were investigated, with a nominal density varying in the range of about 1-5∙10 20 cm -3 and subjected to two different high temperature thermal treatments. One annealing method uses a radiofrequency heated furnace till to 1950°C (Conventional Annealing, CA), the other exploits a microwave field, providing a fast heating rate up to 2000°C (Micro-Wave Annealing, MWA). In this contest, mainly ion implanted p-type samples were investigated, both off-axis and on-axis <0001> semi-insulating 4H-SiC. Concerning p-type off-axis samples, a high electrical activation of implanted Al (50-70%) and a compensation ratio below 10% were estimated. In the work, the main sample processing parameters have been varied, as the implant temperature, CA annealing duration, and heating/cooling rates, and the best values assessed. MWA method leads to higher hole density and lower mobility than CA in equivalent ion implanted layers, resulting in lower resistivity, probably related to the 50°C higher annealing temperature. An optimal duration of the CA treatment was estimated in about 12-13 minutes. A RT resistivity on the lowest reported in literature for this kind of samples, has been obtained. 2) Low resistivity data: variable range hopping Notwithstanding the heavy p-type doping levels, the carrier density remained less than the critical one required for a semiconductor to metal transition. However, the high carrier densities obtained was enough to trigger a low temperature impurity band (IB) conduction. In the heaviest doped samples, such a conduction mechanism persists till to RT, without significantly prejudice the mobility values. This feature can have an interesting technological fall, because it guarantee a nearly temperature- independent carrier density, it being not affected by freeze-out effects. The usual transport mechanism occurring in the IB conduction is the nearest neighbor hopping: such a regime is effectively consistent with the resistivity temperature behavior of the lowest doped samples. In the heavier doped samples, however, a trend of the resistivity data compatible with a variable range hopping (VRH) conduction has been pointed out, here highlighted for the first time in p-type 4H-SiC. Even more: in the heaviest doped samples, and in particular, in those annealed by MWA, the temperature dependence of the resistivity data is consistent with a reduced dimensionality (2D) of the VRH conduction. In these samples, TEM investigation pointed out faulted dislocation loops in the basal plane, whose average spacing along the c-axis is comparable with the optimal length of the hops in the VRH transport. This result suggested the assignment of such a peculiar behavior to a kind of spatial confinement into a plane of the carrier hops. 3) Test device the p + -n junction In the last part of the work, the electrical properties of 4H-SiC diodes were also studied. In this case, a heavy Al + ion implantation was realized on n-type epilayers, according to the technological process applied for final devices. Good rectification properties was shown from these preliminary devices in their current-voltage characteristics. Admittance spectroscopy and deep level transient spectroscopy measurements showed the presence of electrically active defects other than the dopants ones, induced in the active region of the diodes by ion implantation. A critical comparison with the literature of these defects was performed. Preliminary to such an investigation, it was assessed the experimental set up for the admittance spectroscopy and current-voltage investigation and the automatic control of these measurements.

Well posedness of an integrodifferential kinetic model of Fokker-Planck type for angiogenesis.

Tumor induced angiogenesis processes including the effect of stochastic motion and branching of blood vessels can be described coupling a (nonlocal in time) integrodifferential kinetic equation of Fokker–Planck type with a diffusion equation for the tumor induced ingiogenic factor. The chemotactic force field depends on the flux of blood vessels through the angiogenic factor. We develop an existence and uniqueness theory for this system under natural assumptions on the initial data. The proof combines the construction of fundamental solutions for associated linearized problems with comparison principles, sharp estimates of the velocity integrals and compactness results for this type of kinetic and parabolic operators

The Gaia-ESO Survey: The analysis of high-resolution UVES spectra of FGK-type stars

Context. The ongoing Gaia-ESO Public Spectroscopic Survey is using FLAMES at the VLT to obtain high-quality medium-resolution Giraffe spectra for about 105 stars and high-resolution UVES spectra for about 5000 stars. With UVES, the Survey has already observed 1447 FGK-type stars. Aims. These UVES spectra are analyzed in parallel by several state-of-the-art methodologies. Our aim is to present how these analyses were implemented, to discuss their results, and to describe how a final recommended parameter scale is defined. We also discuss the precision (method-to-method dispersion) and accuracy (biases with respect to the reference values) of the final parameters. These results are part of the Gaia-ESO second internal release and will be part of its first public release of advanced data products. Methods. The final parameter scale is tied to the scale defined by the Gaia benchmark stars, a set of stars with fundamental atmospheric parameters. In addition, a set of open and globular clusters is used to evaluate the physical soundness of the results. Each of the implemented methodologies is judged against the benchmark stars to define weights in three different regions of the parameter space. The final recommended results are the weighted medians of those from the individual methods. Results. The recommended results successfully reproduce the atmospheric parameters of the benchmark stars and the expected Teff-log  g relation of the calibrating clusters. Atmospheric parameters and abundances have been determined for 1301 FGK-type stars observed with UVES. The median of the method-to-method dispersion of the atmospheric parameters is 55 K for Teff, 0.13 dex for log  g and 0.07 dex for [Fe/H]. Systematic biases are estimated to be between 50−100 K for Teff, 0.10−0.25 dex for log  g and 0.05−0.10 dex for [Fe/H]. Abundances for 24 elements were derived: C, N, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ba, Nd, and Eu. The typical method-to-method dispersion of the abundances varies between 0.10 and 0.20 dex. Conclusions. The Gaia-ESO sample of high-resolution spectra of FGK-type stars will be among the largest of its kind analyzed in a homogeneous way. The extensive list of elemental abundances derived in these stars will enable significant advances in the areas of stellar evolution and Milky Way formation and evolution.

The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical active site serine residue instead of a catalytic cysteine. Members of this SERAser subfamily are abundantly expressed in asexual blood stages, rendering them attractive drug and vaccine targets. In this study, we show by antibody localization and in vivo fluorescent tagging with the red fluorescent protein mCherry that the two P. berghei serine-type family members, PbSERA1 and PbSERA2, display differential expression towards the final stages of merozoite formation. Via targeted gene replacement, we generated single and double gene knockouts of the P. berghei SERAser genes. These loss-of-function lines progressed normally through the parasite life cycle, suggesting a specialized, non-vital role for serine-type SERAs in vivo. Parasites lacking PbSERAser showed increased expression of the cysteine-type PbSERA3. Compensatory mechanisms between distinct SERA subfamilies may thus explain the absence of phenotypical defect in SERAser disruptants, and challenge the suitability to develop potent antimalarial drugs based on specific inhibitors of Plasmodium serine-type SERAs.

Forest products research guide in fundamental and applied research.

"The first edition was issued in 1943 under the title 'Bibliography of fundamental and applied research in forest products'."

Merging of low-mass systems and the origin of the Fundamental Plane

We present a new set of dissipationless N-body simulations to examine the feasibility of creating bright ellipticals (following the Kormendy relation, hereafter KR) by hierarchically merging present-day early-type dwarf galaxies, and to study how the encounter parameters affect the location of the end product in the (mu(e))-R-e plane. We investigate the merging of one-component galaxies of both equal and different masses, the merging of two-component galaxy models to explore the effect of dark haloes on the final galaxy characteristics, and the merging of ultracompact dwarf galaxies. We find that the increase of (mu(e)) with R-e is attributable to an increase in the initial orbital energy. The merger remnants shift down in the (mu(e))-R-e plane and fail to reach the KR. Thus, the KR is not reproducible by mergers of dwarf early-type systems, rendering untenable the theory that present-day dwarfs are responsible for even a small fraction of the present-day ellipticals, unless a considerable amount of dissipation is invoked. However, we do find that present-day dwarfs can be formed by the merger of ultracompact dwarfs.

Unexpected role of surface transglutaminase type II in celiac disease

Background & Aims: In celiac disease (CD), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach. Methods: Duodenal biopsy specimens from 30 treated patients with CD, 33 untreated patients with CD, and 24 controls were cultured with or without gliadin peptides p31-43, pα-9, and deamidated pα-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis. Results: The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells. Conclusions: These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in CD. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases. © 2005 by the American Gastroenterological Association.

Fundamental mechanisms affecting service performance of electroplated plastics

Ten grades of ABS and four grades of polypropylene have been plated with various copper + nickel + chromium coatings and subjected to a variety of tests. In corrosion studies the pre-electroplating sequence and plastics type have been shown to influence performance. One ABS pre-electroplating sequence was consistently associated with better corrosion performance; two factors were responsible for this, namely the more severe nature of the etch and the relatively more noble electroless nickel. Statistical analysis has indicated that order of severity of the corrosion tests was static-mobile-CASS, the latter being the least severe. In mechanical tests two properties of ABS and polypropJylene, ductility and impact strength, have been shown to be adversely affected when electrodeposited layers were applied. The cause of this is due to a complex of factors, the most important of which is the notch sensitivity of the plastics. Peel adhesion has been studied on flat panels and also on ones which had a ridge and a valley moulded into one face. High adhesion peaks occurred on the flat face at regions associated with the ridge and valley. The local moulding conditions induced by the features were responsible for this phenonemon. In the main programme the thermal cycling test was shown to be more likely than the peel adhesion test to give an indication of the service performance of electroplated plastics.

The method of fundamental solutions for free surface Stefan problems

In this paper, free surface problems of Stefan-type for the parabolic heat equation are investigated using the method of fundamental solutions. The additional measurement necessary to determine the free surface could be a boundary temperature, a heat flux or an energy measurement. Both one- and two-phase flows are investigated. Numerical results are presented and discussed.

Waveform type evaluation in congenital nystagmus

Congenital nystagmus is an ocular-motor disorder characterised by involuntary, conjugated and bilateral to and fro ocular oscillations. In this study a method to recognise automatically jerk waveform inside a congenital nystagmus recording and to compute foveation time and foveation position variability is presented. The recordings were performed with subjects looking at visual targets, presented in nine eye gaze positions; data were segmented into blocks corresponding to each gaze position. The nystagmus cycles were identified searching for local minima and maxima (SpEp sequence) in intervals centred on each slope change of the eye position signal (position criterion). The SpEp sequence was then refined using an adaptive threshold applied to the eye velocity signal; the outcome is a robust detection of each slow phase start point, fundamental to accurately compute some nystagmus parameters. A total of 1206 slow phases was used to compute the specificity in waveform recognition applying only the position criterion or adding the adaptive threshold; results showed an increase in negative predictive value of 25.1% using both features. The duration of each foveation window was measured on raw data or using an interpolating function of the congenital nystagmus slow phases; foveation time estimation less sensitive to noise was obtained in the second case. © 2010.

Polynomials of Pellian Type and Continued Fractions

We investigate infinite families of integral quadratic polynomials {fk (X)} k∈N and show that, for a fixed k ∈ N and arbitrary X ∈ N, the period length of the simple continued fraction expansion of √fk (X) is constant. Furthermore, we show that the period lengths of √fk (X) go to infinity with k. For each member of the families involved, we show how to determine, in an easy fashion, the fundamental unit of the underlying quadratic field. We also demonstrate how the simple continued fraction ex- pansion of √fk (X) is related to that of √C, where √fk (X) = ak*X^2 +bk*X + C. This continues work in [1]–[4].

Weighted Theorems on Fractional Integrals in the Generalized Hölder Spaces via Indices mω and Mω

Mathematics Subject Classification: 26A16, 26A33, 46E15.

Theorems on the Convergence of Series in Generalized Lommel-Wright Functions

Mathematics Subject Classification: 30B10, 30B30; 33C10, 33C20